Other surgical risk scores, such as the logistic EuroSCORE, while correlated with overall prediction of risk, are poorly calibrated to estimate precise

sAVR mortality rates.4 Table 1 ACC-AHA recommendations for surgical aortic valve replacement.3 Many patients during cannot undergo sAVR due to excessive surgical risk, including porcelain aorta,5, 6 hostile Inhibitors,research,lifescience,medical mediastinum, severe lung or liver disease, frailty, renal failure,7-9 advanced age, and prior CABG,10 among other factors,11, 12 many of which are not included in current surgical risk assessment algorithms. In patients who are deemed unsuitable for sAVR due to comorbidities, transcatheter aortic valve replacement (TAVR) has been used as an alternative to relieve Inhibitors,research,lifescience,medical symptoms and extend life. Almost 50,000 patients have been treated worldwide with one of the two commercially approved TAVR devices, including the balloon-expandable Edwards SAPIEN Transcatheter Heart Valve (Edwards LifeSciences, Irvine, California) and the self-expanding CoreValve Revalving System (Medtronic, Minneapolis, Minnesota). A Ponatinib number of additional

transfemoral and transapical devices are under evaluation. Inhibitors,research,lifescience,medical The purpose of this report is to review the clinical trials used to evaluate TAVR in patients who are at higher risk for sAVR. The clinical evidence base includes both prospective registries and randomized clinical trials. Future trial designs evaluating TAVR in intermediate populations will Inhibitors,research,lifescience,medical also be discussed. Extreme-Risk or Inoperable Patients for sAVR Early clinical evaluation of TAVR included patients deemed unsuitable for sAVR. The logistic Euroscore was the primary risk algorithm used for reporting these series, but a number Inhibitors,research,lifescience,medical of specific clinical factors, including advanced age, prior CABG, cirrhosis, pulmonary disease and pulmonary artery hypertension, right ventricular failure, or mediastinal radiation were used for inclusion

of patients in TAVR studies. Balloon-Expandable TAVR Drug_discovery Registries and Randomized Clinical Trials The Edwards SAPIEN Transcatheter Heart Valve consists of a trileaflet bovine pericardial valve and a balloon-expandable, stainless-steel support frame. The SAPIEN valve has undergone clinical study in the United States in 23-mm and 26-mm sizes. It is placed by means of a 22-French (Fr) or 24-Fr sheath from the femoral artery or via the transapical approach using a modified frame and larger delivery sheath. A second-generation 18-Fr RetroFlex II delivery system and a 29-mm SAPIEN XT valve are both available outside the United States and are currently undergoing US-based clinical trials through the PARTNER II study. A number of single-center series have evaluated the outcomes of TAVR using the Edwards SAPIEN system.